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Sepsis Updates
The Third
International
Consensus ( 2016 )
Sepsis 3
Dr. Ashraf Nadeem
MD , Critical Care Medicine
Head of ICU
Hafr Elbatin Central Hospital
Saudi Arabia
The Rory story !!!
An infection , unnoticed , turn Unstoppable• In March 2012, Rory
Staunton, a 12-year-old boy in
Queens, New York, cut his arm
playing basketball in school.
The next day, his parents,
worried about his fever and leg
pain, took him to see his
pediatrician and then, the day
after, to the emergency
department at Langone
Medical Center. He was
discharged with a diagnosis of
an upset stomach and
dehydration but died 3 days
later from sepsis
Key Concepts of Sepsis
• Sepsis is the primary cause of death from infection,
especially if not recognized and treated promptly. Its
recognition mandates urgent attention.
• Sepsis is a syndrome shaped by pathogen factors
and host factors (eg, sex, race and other genetic
determinants, age, comorbidities, environment)
with characteristics that evolve over time.
• What differentiates sepsis from infection is an
aberrant or dysregulated host response and the
presence of organ dysfunction.
Key Concepts of Sepsis
• Sepsis-induced organ dysfunction may be occult;
therefore, its presence should be considered in
any patient presenting with infection.
Conversely, unrecognized infection may be the
cause of new-onset organ dysfunction.
• Any unexplained organ dysfunction should thus
raise the possibility of underlying infection.
Key Concepts of Sepsis
• The clinical and biological phenotype of sepsis
can be modified by preexisting acute illness,
long-standing comorbidities, medication, and
interventions.
• Specific infections may result in local organ
dysfunction without generating a dysregulated
systemic host response.
Why Sepsis again !!
Why new definitions !!
Why new scoring system !!
Why Sepsis is revisited again !!!
• It is still an economic burden on public health
▫ $ 20 billion of total US hospital cost 2011 (Torio et
al)
▫ Saudi Arabia ???
• Sepsis is the leading cause of death in non-
coronary care intensive care units, with a
mortality rate between 30-50%
Why Sepsis is revisited again !!!
• From 2007 to 2009 , over 2,047,038 patients
were admitted with a sepsis-related illness
▫ 54% are diagnosed in the ED
▫ 34% on the hospital wards
▫ 13% in the ICU
Hospitalization rates
Incidence and Cost
Why Sepsis again !!
Why new definitions !!
Why new scoring system !!
The old definitions



Why new definitions
• Definitions of sepsis and septic shock were last
revised in 2001. Considerable advances have
since been made into the pathobiology
(changes in organ function, morphology, cell
biology, biochemistry, immunology, and
circulation), management, and epidemiology of
sepsis, suggesting the need for reexamination.
Why new definitions !!
• To know what distinguishes sepsis from
uncomplicated infection as simple infection
(which could simply controlled by rest and cup
of hot tea!! ) SIRS criteria basically could be the
same
“We need to differentiate a straightforward
infection from one that can cause organ
dysfunction or death”
The overlap SIRS, infection, sepsis
and inflammation
Why Sepsis again !!
Why new definitions !!
Why new scoring system !!
The Validity of SIRS challenged
• SIRS criteria have been used to diagnose sepsis
for more than 20 years.
• “SIRS no longer has any legs ….. It sounded like
a good idea in 1990 , but it has lost steam…..”
• Poor concurrent Validity
SIRS Criteria
• Two or more of:
▫ Temperature >38°C or <36°C
▫ Heart rate >90/min
▫ Respiratory rate >20/min or PaCO2 <32 mm Hg
(4.3 kPa)
▫ White blood cell count >12 000/mm3 or
<4000/mm3 or >10% immature bands
 Bone et al.Crit Care Med. 1992;20(6):864-874.
Sequential [Sepsis-Related] Organ
Failure Assessment Score
Timothy Buchman, MD, from Emory University in Atlanta
The care in sepsis is focused on prompt recognition and early
treatment. “Shift of focus from inflammation to Organ Dysfunction ”
Introduction
• This is one of the largest collaborative studies
ever conducted in the field of critical care
medicine. It is also one of the first studies of
electronic health records in field of Intensive
care.
Introduction
• Focused primarily on patients in the intensive
care unit who were receiving antibiotics and
fluid cultures, as those were the patients who
were thought to be infected.
• The team analyzed 148,907 patients with
suspected infection, and evaluated how well the
existing and the new criteria predicted sepsis
mortality in these patients.
The Process of Developing New
Definitions
The co-chairs
Drs Deutschman & Singer)
• A task force of 19 critical
care, infectious disease,
surgical, and pulmonary
specialists in January
2014.
• The group engaged in
iterative discussions via
face-to-face meetings
between January 2014
and January 2015
The process
• Definitions and clinical criteria were generated
through meetings, Delphi processes, analysis of
electronic health record databases, and voting,
followed by circulation to international
professional societies, requesting peer review
and endorsement (by 31 societies listed in the
Acknowledgment).
Summary of Data Sets
Accrual of Encounters for Primary Cohort
What clinical criteria to study
New definitions ( the screening tool )
• Patients with suspected infection who are likely
to have a prolonged ICU stay or to die in the
hospital can be promptly identified at the
bedside with qSOFA,
▫ Respiratory rate ≥22/min
▫ Altered mentation
▫ Systolic blood pressure ≤ 100mmHg
 The presence of at least two of these criteria
strongly predicts the likelihood of poor
outcome in out-of-ICU patients with clinical
suspicion of sepsis.
New definitions
• Sepsis is defined as life-threatening organ
dysfunction caused by a dysregulated host
response to infection.
• NB:
▫ The SIRS criteria have been removed
▫ It may present in simple, non-complicated
infection, or in response to non infectious-triggers
(i.e. trauma, pancreatitis, post-cardiac arrest
syndrome),
▫ Or may even be absent in critically ill patients with
obvious evidence of a life-threatening infection.
New definitions
• Organ dysfunction can be identified as an acute
change in total SOFA score> 2 points
consequent to the infection.
• A SOFA score > 2 reflects an overall mortality
risk of approximately 10% in a general hospital
population with suspected infection
• The baseline SOFA score can be assumed to be
zero or in patients not known to have preexisting
organ dysfunction.
New definitions
• Septic shock is a subset of sepsis in which
underlying circulatory and cellular/metabolic
abnormalities are profound enough to
substantially increase mortality.
▫ Clinical criteria identifying such condition include the
need for vasopressors to obtain a MAP≥ 65mmHg and
an increase in lactate concentration > 2 mmol/L, despite
adequate fluid resuscitation.
Terms like Severe Sepsis/Septicemia has been removed
Organ Failure Check Best in the ICU,
Quick Score Better Elsewhere
• In the old criteria for sepsis, the systemic
inflammatory response syndrome score was a
measure of respiratory rate, white blood cell
count, heart rate, and fever.
• The sequential organ failure assessment score
( SOFA ) and the logistic organ dysfunction
system score ( LODS ) are more recent criteria.
Analysis of electronic records
• The receiver operating characteristic curve
(AUROC) has been assessed to predict the
validity of the different scores.
• The quick score was a better predictor of
hospital mortality for patients with suspected
infection who were not in the ICU than for those
in the ICU.
Predictive Validity for Death
Area Under the Receiver Operating Characteristic Curve and
95%Confidence Intervals for In-Hospital Mortality of Candidate Criteria
(SIRS, SOFA, LODS, and qSOFA) Among Suspected Infection Encounters
in the UPMC Validation Cohort (N = 74 454)
Which score to use !!
• "The SOFA score found patients more likely to
be septic both in and out of the ICU. But it
involves the use of many lab tests and is a bit
complex.
• For patients not in the ICU, the performance of
Quick SOFA score was similar to that of the
sequential organ failure assessment score.
Recommendation
• Infection plus two or more sequential organ
failure assessment points, and the use of quick
sepsis-related organ failure assessment score as
a prompt to identify patients likely to be septic
early on,.
A Need for Sepsis Definitions for the Public
and for Health Care Practitioners
• A life-threatening condition that arises when the
body’s response to infection injures its own
tissue.
• Finally, all these new definitions are
recommended for coding and research
purposes.
Terminology and international
classification of disease Coding
Recommended primary ICD codes
Sepsis Septic shock
Controversies and limitations
• Most data extracted from US database
• q SOFA and SOFA can miss occult organ
dysfunction
• Specific infections can cause local organ
dysfunction without dysregulated systemic host
response
• Non- availability of lactate measurements in
resource poor settings
• Task force focused on adult patients
Operationalization of clinical Criteria identifying
patients with sepsis & septic shock
Fostering future updates.
• Despite the unavoidable limits affecting any
definition of syndromes that do not have any
specific diagnostic clinical, imaging, laboratory
or biochemical marker, this new classification
includes the most recent deep understanding of
sepsis biology and stresses the clinical relevance
of organ dysfunction. In addition, similarly to
software updates, the Sepsis-3 definition has
been established with the aim of fostering future
updates.
Conclusions
• Among ICU encounters with suspected infection, the
predictive validity for in-hospital mortality of SOFA
was not significantly different than the more
complex LODS but was statistically greater than
SIRS and qSOFA, supporting its use in clinical
criteria for sepsis.
• Among encounters with suspected infection outside
of the ICU, the predictive validity for in-hospital
mortality of qSOFA was statistically greater than
SOFA and SIRS, supporting its use as a prompt to
consider possible sepsis.
Take Home Message
• New definitions of sepsis and septic shock are now
available. These rely on the importance of recognizing
when an adaptive and protective host response becomes
maladaptive, impairing organ function.
• SIRS criteria may still guide clinicians toward identifying
an ongoing infectious process, but ‘severe sepsis’ is no
longer a part of the new classification.
• Hypotension and lactate level are key points
underpinning the new septic shock criteria, as they
reflect metabolic and cellular abnormalities
characterizing the pathobiology of sepsis.
Finally
“It took us more than 10 years to understand
sepsis , now we will have to change it all ……”
“…… Is it the final word in sepsis .. ? … or the
starting point of discussion and additional
research into this deadly condition ”
 Julie A. Jacob, MA JAMA. 2016;315(8):739-740.
doi:10.1001/jama.2016.0736.
Sepsis updates 2016

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Sepsis updates 2016

  • 1. Sepsis Updates The Third International Consensus ( 2016 ) Sepsis 3 Dr. Ashraf Nadeem MD , Critical Care Medicine Head of ICU Hafr Elbatin Central Hospital Saudi Arabia
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  • 3. The Rory story !!! An infection , unnoticed , turn Unstoppable• In March 2012, Rory Staunton, a 12-year-old boy in Queens, New York, cut his arm playing basketball in school. The next day, his parents, worried about his fever and leg pain, took him to see his pediatrician and then, the day after, to the emergency department at Langone Medical Center. He was discharged with a diagnosis of an upset stomach and dehydration but died 3 days later from sepsis
  • 4. Key Concepts of Sepsis • Sepsis is the primary cause of death from infection, especially if not recognized and treated promptly. Its recognition mandates urgent attention. • Sepsis is a syndrome shaped by pathogen factors and host factors (eg, sex, race and other genetic determinants, age, comorbidities, environment) with characteristics that evolve over time. • What differentiates sepsis from infection is an aberrant or dysregulated host response and the presence of organ dysfunction.
  • 5. Key Concepts of Sepsis • Sepsis-induced organ dysfunction may be occult; therefore, its presence should be considered in any patient presenting with infection. Conversely, unrecognized infection may be the cause of new-onset organ dysfunction. • Any unexplained organ dysfunction should thus raise the possibility of underlying infection.
  • 6. Key Concepts of Sepsis • The clinical and biological phenotype of sepsis can be modified by preexisting acute illness, long-standing comorbidities, medication, and interventions. • Specific infections may result in local organ dysfunction without generating a dysregulated systemic host response.
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  • 8. Why Sepsis again !! Why new definitions !! Why new scoring system !!
  • 9. Why Sepsis is revisited again !!! • It is still an economic burden on public health ▫ $ 20 billion of total US hospital cost 2011 (Torio et al) ▫ Saudi Arabia ??? • Sepsis is the leading cause of death in non- coronary care intensive care units, with a mortality rate between 30-50%
  • 10. Why Sepsis is revisited again !!! • From 2007 to 2009 , over 2,047,038 patients were admitted with a sepsis-related illness ▫ 54% are diagnosed in the ED ▫ 34% on the hospital wards ▫ 13% in the ICU
  • 13. Why Sepsis again !! Why new definitions !! Why new scoring system !!
  • 15. Why new definitions • Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
  • 16. Why new definitions !! • To know what distinguishes sepsis from uncomplicated infection as simple infection (which could simply controlled by rest and cup of hot tea!! ) SIRS criteria basically could be the same “We need to differentiate a straightforward infection from one that can cause organ dysfunction or death”
  • 17. The overlap SIRS, infection, sepsis and inflammation
  • 18. Why Sepsis again !! Why new definitions !! Why new scoring system !!
  • 19. The Validity of SIRS challenged • SIRS criteria have been used to diagnose sepsis for more than 20 years. • “SIRS no longer has any legs ….. It sounded like a good idea in 1990 , but it has lost steam…..” • Poor concurrent Validity
  • 20. SIRS Criteria • Two or more of: ▫ Temperature >38°C or <36°C ▫ Heart rate >90/min ▫ Respiratory rate >20/min or PaCO2 <32 mm Hg (4.3 kPa) ▫ White blood cell count >12 000/mm3 or <4000/mm3 or >10% immature bands  Bone et al.Crit Care Med. 1992;20(6):864-874.
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  • 24. Timothy Buchman, MD, from Emory University in Atlanta The care in sepsis is focused on prompt recognition and early treatment. “Shift of focus from inflammation to Organ Dysfunction ”
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  • 28. Introduction • This is one of the largest collaborative studies ever conducted in the field of critical care medicine. It is also one of the first studies of electronic health records in field of Intensive care.
  • 29. Introduction • Focused primarily on patients in the intensive care unit who were receiving antibiotics and fluid cultures, as those were the patients who were thought to be infected. • The team analyzed 148,907 patients with suspected infection, and evaluated how well the existing and the new criteria predicted sepsis mortality in these patients.
  • 30. The Process of Developing New Definitions The co-chairs Drs Deutschman & Singer) • A task force of 19 critical care, infectious disease, surgical, and pulmonary specialists in January 2014. • The group engaged in iterative discussions via face-to-face meetings between January 2014 and January 2015
  • 31. The process • Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).
  • 33. Accrual of Encounters for Primary Cohort
  • 35. New definitions ( the screening tool ) • Patients with suspected infection who are likely to have a prolonged ICU stay or to die in the hospital can be promptly identified at the bedside with qSOFA, ▫ Respiratory rate ≥22/min ▫ Altered mentation ▫ Systolic blood pressure ≤ 100mmHg  The presence of at least two of these criteria strongly predicts the likelihood of poor outcome in out-of-ICU patients with clinical suspicion of sepsis.
  • 36. New definitions • Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. • NB: ▫ The SIRS criteria have been removed ▫ It may present in simple, non-complicated infection, or in response to non infectious-triggers (i.e. trauma, pancreatitis, post-cardiac arrest syndrome), ▫ Or may even be absent in critically ill patients with obvious evidence of a life-threatening infection.
  • 37. New definitions • Organ dysfunction can be identified as an acute change in total SOFA score> 2 points consequent to the infection. • A SOFA score > 2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection • The baseline SOFA score can be assumed to be zero or in patients not known to have preexisting organ dysfunction.
  • 38. New definitions • Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. ▫ Clinical criteria identifying such condition include the need for vasopressors to obtain a MAP≥ 65mmHg and an increase in lactate concentration > 2 mmol/L, despite adequate fluid resuscitation. Terms like Severe Sepsis/Septicemia has been removed
  • 39. Organ Failure Check Best in the ICU, Quick Score Better Elsewhere • In the old criteria for sepsis, the systemic inflammatory response syndrome score was a measure of respiratory rate, white blood cell count, heart rate, and fever. • The sequential organ failure assessment score ( SOFA ) and the logistic organ dysfunction system score ( LODS ) are more recent criteria.
  • 40.
  • 41. Analysis of electronic records • The receiver operating characteristic curve (AUROC) has been assessed to predict the validity of the different scores. • The quick score was a better predictor of hospital mortality for patients with suspected infection who were not in the ICU than for those in the ICU.
  • 43. Area Under the Receiver Operating Characteristic Curve and 95%Confidence Intervals for In-Hospital Mortality of Candidate Criteria (SIRS, SOFA, LODS, and qSOFA) Among Suspected Infection Encounters in the UPMC Validation Cohort (N = 74 454)
  • 44. Which score to use !! • "The SOFA score found patients more likely to be septic both in and out of the ICU. But it involves the use of many lab tests and is a bit complex. • For patients not in the ICU, the performance of Quick SOFA score was similar to that of the sequential organ failure assessment score.
  • 45. Recommendation • Infection plus two or more sequential organ failure assessment points, and the use of quick sepsis-related organ failure assessment score as a prompt to identify patients likely to be septic early on,.
  • 46. A Need for Sepsis Definitions for the Public and for Health Care Practitioners • A life-threatening condition that arises when the body’s response to infection injures its own tissue. • Finally, all these new definitions are recommended for coding and research purposes.
  • 48. Recommended primary ICD codes Sepsis Septic shock
  • 49. Controversies and limitations • Most data extracted from US database • q SOFA and SOFA can miss occult organ dysfunction • Specific infections can cause local organ dysfunction without dysregulated systemic host response • Non- availability of lactate measurements in resource poor settings • Task force focused on adult patients
  • 50. Operationalization of clinical Criteria identifying patients with sepsis & septic shock
  • 51. Fostering future updates. • Despite the unavoidable limits affecting any definition of syndromes that do not have any specific diagnostic clinical, imaging, laboratory or biochemical marker, this new classification includes the most recent deep understanding of sepsis biology and stresses the clinical relevance of organ dysfunction. In addition, similarly to software updates, the Sepsis-3 definition has been established with the aim of fostering future updates.
  • 52. Conclusions • Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. • Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.
  • 53. Take Home Message • New definitions of sepsis and septic shock are now available. These rely on the importance of recognizing when an adaptive and protective host response becomes maladaptive, impairing organ function. • SIRS criteria may still guide clinicians toward identifying an ongoing infectious process, but ‘severe sepsis’ is no longer a part of the new classification. • Hypotension and lactate level are key points underpinning the new septic shock criteria, as they reflect metabolic and cellular abnormalities characterizing the pathobiology of sepsis.
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  • 55. Finally “It took us more than 10 years to understand sepsis , now we will have to change it all ……” “…… Is it the final word in sepsis .. ? … or the starting point of discussion and additional research into this deadly condition ”  Julie A. Jacob, MA JAMA. 2016;315(8):739-740. doi:10.1001/jama.2016.0736.

Notas del editor

  1. Sepsis is now defined as a ‘life-threatening organ dysfunction due to a dysregulated host response to infection’. In this new definition the concept of the non-homeostatic host response to infection is strongly stressed while the SIRS criteria have been removed. The SIRS criteria are considered overly non-specific and of poor clinical utility: i.e. they may be present in simple, non-complicated infection, or in response to non infectious-triggers (i.e. trauma, pancreatitis, post-cardiac arrest syndrome), or may even be absent in critically ill patients with obvious evidence of a life-threatening infection. While recognition and treatment of the infectious trigger obviously remain important, the attention with sepsis is now more focused on the pathobiology of the host response and the related organ dysfunction. The inflammatory response accompanying infection (pyrexia, neutrophilia, etc) often represent an appropriate host response to any infection, and this may not necessarily be life-threatening
  2. Sepsis is now defined as a ‘life-threatening organ dysfunction due to a dysregulated host response to infection’. In this new definition the concept of the non-homeostatic host response to infection is strongly stressed while the SIRS criteria have been removed. The SIRS criteria are considered overly non-specific and of poor clinical utility: i.e. they may be present in simple, non-complicated infection, or in response to non infectious-triggers (i.e. trauma, pancreatitis, post-cardiac arrest syndrome), or may even be absent in critically ill patients with obvious evidence of a life-threatening infection. While recognition and treatment of the infectious trigger obviously remain important, the attention with sepsis is now more focused on the pathobiology of the host response and the related organ dysfunction. The inflammatory response accompanying infection (pyrexia, neutrophilia, etc) often represent an appropriate host response to any infection, and this may not necessarily be life-threatening
  3. This new definition is mainly focused on the importance to both distinguish septic shock from other forms of circulatory shock and underline the detrimental clinical impact of sepsis-induced cellular metabolism abnormalities.